We tested a report that atrial natriuretic peptide (ANP) injected into, or near, the subfornical organ (SFO) will reduce the water consumption of previously water deprived rats and that suggested ANP acts on neurons in the SFO to bring about this action. We tested this suggestion and the hypothesis that the SFO is involved in the facilitation of drinking produced by opioids. ANP (5 nmol in 4 microliters, IVT) or naloxone (2 mg/ml/kg, SC, or 200 micrograms in 2 microliters, IVT) when given to rats deprived of water for 16 h (SC treatment) or 23 h (IVT treatment) significantly depressed postdeprivation drinking measured at 15 and 60 min. Rats with complete, partial, or control lesions of the SFO, after the same treatment, also showed a significant depression of postdeprivation drinking and, after 23-h deprivation, a significant hyperdipsia. There was no interaction between drug effects and lesion effects (two-factor analysis of variance, Tukey's post-hoc tests). The hyperdipsia declined exponentially and was lost 45-50 days after lesioning. Our results do not support the hypothesis that the SFO is involved in the actions of ANP or of opioids on postdeprivation drinking.